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Yorodumi- PDB-7x8z: The SARS-CoV-2 receptor binding domain bound with the Fab fragmen... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7x8z | ||||||
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Title | The SARS-CoV-2 receptor binding domain bound with the Fab fragment of a human neutralizing antibody Ab188 | ||||||
Components |
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Keywords | VIRAL PROTEIN / severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike trimer / COVID-19 / human neutralizing antibody / RBD | ||||||
Function / homology | Function and homology information Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell ...Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / membrane fusion / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / identical protein binding / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | ||||||
Authors | Kamada, K. / Shirouzu, M. | ||||||
Funding support | Japan, 1items
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Citation | Journal: iScience / Year: 2022 Title: Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models. Authors: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Tomomi Uchikubo-Kamo / Yuri Tomabechi / Kazuharu Hanada / Saya Moriyama / Yoshimasa ...Authors: Masaru Takeshita / Hidehiro Fukuyama / Katsuhiko Kamada / Takehisa Matsumoto / Chieko Makino-Okamura / Tomomi Uchikubo-Kamo / Yuri Tomabechi / Kazuharu Hanada / Saya Moriyama / Yoshimasa Takahashi / Hirohito Ishigaki / Misako Nakayama / Cong Thanh Nguyen / Yoshinori Kitagawa / Yasushi Itoh / Masaki Imai / Tadashi Maemura / Yuri Furusawa / Hiroshi Ueki / Kiyoko Iwatsuki-Horimoto / Mutsumi Ito / Seiya Yamayoshi / Yoshihiro Kawaoka / Mikako Shirouzu / Makoto Ishii / Hideyuki Saya / Yasushi Kondo / Yuko Kaneko / Katsuya Suzuki / Koichi Fukunaga / Tsutomu Takeuchi / Abstract: The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In ...The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from patients with COVID-19-convalescent, and identified antibodies that exhibited the comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To prevent antibody-dependent enhancement, N297A modification was introduced. Our antibodies showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7x8z.cif.gz | 182.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7x8z.ent.gz | 124.1 KB | Display | PDB format |
PDBx/mmJSON format | 7x8z.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7x8z_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7x8z_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7x8z_validation.xml.gz | 24.9 KB | Display | |
Data in CIF | 7x8z_validation.cif.gz | 35.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x8/7x8z ftp://data.pdbj.org/pub/pdb/validation_reports/x8/7x8z | HTTPS FTP |
-Related structure data
Related structure data | 33061MC 7x8wC 7x8yC 7x90C 7x91C 7x92C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 141459.453 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: From aa1209, additional tags are added at the C-terminal, with Foldon sequence, TEV(tobacco etch virus) protease recognition and cleavage site, AviTag(peptide that allows for enzymatic ...Details: From aa1209, additional tags are added at the C-terminal, with Foldon sequence, TEV(tobacco etch virus) protease recognition and cleavage site, AviTag(peptide that allows for enzymatic biotinylation),and 6xHis affinity tag. Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Gene: S, 2 / Production host: Homo sapiens (human) / References: UniProt: P0DTC2 |
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#2: Antibody | Mass: 28637.084 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Production host: Homo sapiens (human) |
#3: Antibody | Mass: 27390.527 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2 Production host: Homo sapiens (human) |
#4: Sugar | ChemComp-NAG / |
Has ligand of interest | Y |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: The SARS-CoV-2 spike protein bound with the Fab fragment of a human neutralizing antibody Ab354 Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.56 MDa / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | |||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | |||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||
Buffer component |
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Specimen | Conc.: 0.84 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 800 nm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 100 K / Temperature (min): 100 K |
Image recording | Electron dose: 50 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
Image scans | Movie frames/image: 40 |
-Processing
Software |
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 69153 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL / Target criteria: Corelation coefficient | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 5CCK Accession code: 5CCK / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 85.97 Å2 | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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